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Hence mucositis is a serious common side effect and is a condition characterized by pain and inflammation of the surface of the mucosa. Although the mucosa recovers during breaks of and following the radiotherapy course, the recovery will depend on the type of tissue involved and on its location. We present a novel flexible multivariate random effects proportional odds model that takes account of the longitudinal course of oral mucositis at different mouth sites and of the radiation dosage (in terms of cumulative dose). The model is an extension of the<jats:italic>proportional odds model<\/jats:italic>that is used for ordinal response variables. Our model includes the ordinal multivariate response of the mucositis score by site, random intercepts for individuals, and a nonlinear function of cumulative radiation dose. The model allows to test whether sensitivity differs by mouth sites after having adjusted for site\u2010specific cumulative radiation dose. The model also allows to check whether and how the (nonlinear) effect of site\u2010specific dose differs by site. We fit the model to longitudinal patient data from a prospective observation and find that after adjusting for cumulative dose, upper, lower lips, and mouth floor are associated with the lowest mucositis scores and hard and soft palate are associated with the highest mucositis scores. This implies the possibility that tissues at different mouth sites differ in their sensitivity to the toxic effect of radiation.<\/jats:p>","DOI":"10.1002\/bimj.201600142","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T18:08:43Z","timestamp":1499710123000},"page":"1339-1351","source":"Crossref","is-referenced-by-count":5,"title":["A flexible multivariate random effects proportional odds model with application to adverse effects during radiation therapy"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-3742","authenticated-orcid":false,"given":"Nicole H.","family":"Augustin","sequence":"first","affiliation":[{"name":"Department of Mathematical Sciences University of Bath Bath BA2 7AY UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry and Statistics University of Freiburg Stefan\u2010Meier\u2010Str. 26 79104 Freiburg Germany"},{"name":"Freiburg Center for Data Analysis and Modeling University of Freiburg Eckerstr. 1 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemarie","family":"Uhlig","sequence":"additional","affiliation":[{"name":"Section Clinical Studies, Department of Radiation Oncology University Hospital Freiburg Hugstetter Strasse 55 79106 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Hanser","sequence":"additional","affiliation":[{"name":"Section Clinical Studies, Department of Radiation Oncology University Hospital Freiburg Hugstetter Strasse 55 79106 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Henke","sequence":"additional","affiliation":[{"name":"Section Clinical Studies, Department of Radiation Oncology University Hospital Freiburg Hugstetter Strasse 55 79106 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry and Statistics University of Freiburg Stefan\u2010Meier\u2010Str. 26 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,10]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Categorical Data Analysis","author":"Agresti A.","year":"2013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9876.2007.00563.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csda.2012.01.026"},{"key":"e_1_2_8_5_1","unstructured":"Belitz C. 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